Upregulation of inflammatory genes and pathways links obesity to severe COVID-19

Authors

• Joshua Currey, Tulane University
• Calder Ellsworth, Tulane University
• Shamima Khatun Mst, Tulane University
• Chenxiao Wang, Tulane University
• Zheng Chen, Tulane University
• Shumei Liu, Tulane University
• Cecily Midkiff, Tulane University
• Mark Xiao, Tulane University
• Mi Ren, Tulane University
• Fengming Liu, Tulane University
• Mona Elgazzaz, LSU Health Sciences Center - New OrleansFollow
• Sharon Fox, Southeast Louisiana VA Medical Center, New Orleans, LA
• Nicholas J. Maness, Tulane University
• Jay Rappaport, Tulane University
• Eric Lazartigues, LSU Health Sciences Center - New OrleansFollow
• Robert Blair, Tulane University
• Jay Kolls, Tulane University
• Franck Mauvais-Jarvis, Tulane University
• Xuebin Qin, Tulane University

Document Type

Article

Publication Date

6-26-2024

Publication Title

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

Abstract

Obesity is a risk factor for developing severe COVID-19. However, the mechanism underlying obesity-accelerated COVID-19 remains unclear. Here, we report results from a study in which 2–3-month-old K18-hACE2 (K18) mice were fed a western high-fat diet (WD) or normal chow (NC) over 3 months before intranasal infection with a sublethal dose of SARS-CoV2 WA1 (a strain ancestral to the Wuhan variant). After infection, the WD-fed K18 mice lost significantly more body weight and had more severe lung inflammation than normal chow (NC)-fed mice. Bulk RNA-seq analysis of lungs and adipose tissue revealed a diverse landscape of various immune cells, inflammatory markers, and pathways upregulated in the infected WD-fed K18 mice when compared with the infected NC-fed control mice. The transcript levels of IL-6, an important marker of COVID-19 disease severity, were upregulated in the lung at 6–9 days post-infection in the WD-fed mice when compared to NC-fed mice. Transcriptome analysis of the lung and adipose tissue obtained from deceased COVID-19 patients found that the obese patients had an increase in the expression of genes and the activation of pathways associated with inflammation as compared to normal-weight patients (n = 2). The K18 mouse model and human COVID-19 patient data support a link between inflammation and an obesity-accelerated COVID-19 disease phenotype. These results also indicate that obesity-accelerated severe COVID-19 caused by SARS-CoV-2 WA1 infection in the K18 mouse model would be a suitable model for dissecting the cellular and molecular mechanisms underlying pathogenesis.

First Page

1

Last Page

11

Volume

1870

Issue

7

Publisher

Elsevier

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License

Recommended Citation

Currey, Joshua; Ellsworth, Calder; Khatun, Shamima Mst; Wang, Chenxiao; Chen, Zheng; Liu, Shumei; Midkiff, Cecily; Xiao, Mark; Ren, Mi; Liu, Fengming; Elgazzaz, Mona; Fox, Sharon; Maness, Nicholas J.; Rappaport, Jay; Lazartigues, Eric; Blair, Robert; Kolls, Jay; Mauvais-Jarvis, Franck; and Qin, Xuebin, "Upregulation of inflammatory genes and pathways links obesity to severe COVID-19" (2024). School of Graduate Studies Faculty Publications. 538.
https://digitalscholar.lsuhsc.edu/sogs_facpubs/538
10.1016/j.bbadis.2024.167322